Clinical Trials /

A Study of an Intratumoral Oncolytic Virus in Patients With Advanced Metastatic Solid Tumors

NCT03954067

Description:

The purpose of this study is to assess the safety and tolerability of ASP9801 and to determine the recommended phase 2 dose (RP2D). The study will also evaluate antitumor activity, objective response rate, pharmacokinetics and virus shedding of ASP9801.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of an Intratumoral Oncolytic Virus in Patients With Advanced Metastatic Solid Tumors
  • Official Title: A Phase 1, Open-label Study of ASP9801, an Oncolytic Virus, Administered by Intratumoral Injection in Patients With Advanced/Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 9801-CL-0101
  • NCT ID: NCT03954067

Conditions

  • Metastatic Cancer
  • Solid Tumors
  • Advanced Cancer

Interventions

DrugSynonymsArms
ASP9801Dose Escalation - cutaneous or subcutaneous lesions

Purpose

The purpose of this study is to assess the safety and tolerability of ASP9801 and to determine the recommended phase 2 dose (RP2D). The study will also evaluate antitumor activity, objective response rate, pharmacokinetics and virus shedding of ASP9801.

Detailed Description

      The study consists of two parts: dose escalation and recommended phase 2 dose expansion. Each
      part of the study will include two separate groups of participants. Group A will include
      participants who will have cutaneous/subcutaneous tumors injected, and group B will include
      participants who will have visceral tumors injected. The study will consist of the following
      periods: screening, initial treatment period (two 28 day cycles), optional extended treatment
      period (continued 28 day cycles) and a follow up period (safety and survival follow up).
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation - cutaneous or subcutaneous lesionsExperimentalParticipants will receive ASP9801 on days 1 and 15 of 28 day cycles to determine the recommended phase 2 dose. After cycle 2, participants who have not met any discontinuation criteria and receiving clinical benefit may be treated on continuous cycles until treatment discontinuation criteria are met.
  • ASP9801
Dose Escalation - visceral lesionsExperimentalParticipants will receive ASP9801 on days 1 and 15 of 28 day cycles to determine the recommended phase 2 dose. After cycle 2, participants who have not met any discontinuation criteria and receiving clinical benefit may be treated on continuous cycles until treatment discontinuation criteria are met.
  • ASP9801
Dose Expansion - cutaneous or subcutaneous lesionsExperimentalParticipants will receive ASP9801 on days 1 and 15 of 28 day cycles at the dose recommended by the dose escalation phase. After cycle 2, participants who have not met any discontinuation criteria and receiving clinical benefit may be treated on continuous cycles until treatment discontinuation criteria are met.
  • ASP9801
Dose Expansion - visceral lesionsExperimentalParticipants will receive ASP9801 on days 1 and 15 of 28 day cycles at the dose recommended by the dose escalation phase. After cycle 2, participants who have not met any discontinuation criteria and receiving clinical benefit may be treated on continuous cycles until treatment discontinuation criteria are met.
  • ASP9801

Eligibility Criteria

        Inclusion Criteria:

          -  Subject must have histologically- or cytologically-confirmed diagnosis of advanced or
             metastatic solid tumor(s).

          -  Subject has measurable disease as determined by Response Evaluation Criteria in Solid
             Tumors (RECIST) version 1.1. At least 1 lesion must be suitable for intratumoral (IT)
             injection. Lesions for injection must be ≥ 10 mm and ≤ 60 mm in longest diameter.

          -  Subject has progressed on or is not eligible for available standard therapy.

          -  Subject has a predicted life expectancy ≥ 12 weeks.

          -  Subject has at least 2 sites of disease suitable for biopsy and is willing and able to
             undergo required tumor biopsies according to the treating institution's guidelines at
             screening and during study treatment.

          -  Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  A female subject is eligible to participate if she is not pregnant and at least 1 of
             the following conditions applies:

               -  Not a woman of childbearing potential (WOCBP) OR

               -  WOCBP who agrees to follow the contraceptive guidance throughout the treatment
                  period and for at least 180 days after the final study investigational product
                  (IP) administration.

          -  Female subject must agree not to breastfeed starting at screening, and throughout the
             study period and 180 days after the final study IP administration.

          -  Female subject must not donate ova starting at screening, and throughout the study
             period and for 180 days after the final study IP administration.

          -  Male subject must agree to remain abstinent or use a condom throughout the study
             period and for 180 days after the final study IP administration.

          -  Male subject with female partner(s) of childbearing potential must agree to use
             contraception during the treatment period and for at least 180 days after the final
             study IP administration.

          -  Male subject must not donate sperm during the treatment period and for at least 180
             days after the final study IP administration.

          -  Subject must be willing and able to comply with the study requirements including
             prohibited concomitant medication restrictions.

          -  Subject agrees not to participate in another interventional study while receiving
             study IP.

          -  Subject has the ability to understand and the willingness to sign a written informed
             consent document.

        Exclusion Criteria:

          -  Subject has ongoing toxicity ≥ Common Terminology Criteria for Adverse Events (CTCAE)
             grade 2 attributable to prior antineoplastic therapies considered clinically
             significant.

          -  Subject who has had major surgery ≤ 4 weeks of screening.

          -  Subject is concurrently participating in another interventional study or has received
             an investigational product ≤ 30 days or 5 half-lives whichever is shorter, prior to
             first IP administration.

          -  Subject with symptomatic or untreated central nervous system metastases or
             leptomeningeal disease. Subjects with treated symptomatic brain metastases should be
             neurologically stable (for 4 weeks post-treatment and prior to screening) and off
             steroids for at least 2 weeks prior to first IP administration.

          -  Subject with active or prior autoimmune or inflammatory disorders requiring systemic
             therapy within past 2 years (including inflammatory skin conditions or severe eczema,
             inflammatory bowel disease (e.g., colitis or Crohn's disease), diverticulitis (with
             the exception of diverticulosis), celiac disease, systemic lupus erythematosus,
             Sarcoidosis syndrome, Wegener syndrome (granulomatosis with polyangiitis), Graves'
             disease, rheumatoid arthritis, hypophysitis, uveitis, etc.

        The following are exceptions to this criterion:

          -  Subject with vitiligo or alopecia

          -  Subject with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone
             replacement

          -  Any chronic skin condition that does not require systemic therapy

               -  Subject with another malignancy that currently requires treatment.

               -  Subject with tumors encasing major vascular structures such as the carotid
                  artery, tumors adjacent to vital neurovascular structures or tumors in locations
                  that are at high risk for adverse events (AEs) or otherwise not considered
                  appropriate for IT injection.

               -  Subject with inadequate organ and marrow functions meeting any of the below
                  criteria:

          -  Leukocytes < 3000/μL

          -  Absolute neutrophil count < 1500/μL

          -  Platelets < 100,000/μL

          -  Hemoglobin (Hgb) < 9 g/dL

          -  International normalized ratio (INR) > 1.5 × ULN and/or activated partial
             thromboplastin time (aPTT) > 1.5 × institutional normal limits, except for patients in
             Group B (Visceral Lesions) escalation and expansion groups where INR and aPTT must be
             normal

          -  Total Bilirubin (TBL) > 1.5 × institutional normal limits (subjects with known Gilbert
             syndrome who are excluded if TBL > 3.0 × institutional normal limits or direct
             bilirubin > 1.5 × institutional normal limits)

          -  Aspartate aminotransferase (AST) and Alanine transaminase (ALT) > 3.0 × institutional
             normal limits. Subjects with tumors in the liver AST and ALT > 5 × institutional
             normal limits.

          -  Albumin < 3.4 g/dL

          -  Creatinine > 1.5 × institutional normal limits

               -  Subject with a condition requiring systemic treatment with either corticosteroids
                  (> 10 mg daily prednisone equivalents) or other immunosuppressive medications
                  within 14 days of first administration of study IP. Inhaled or topical steroids
                  and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted
                  in the absence of active autoimmune disease.

               -  Subject has an uncontrolled intercurrent illness including, but not limited to,
                  ongoing or active infection, symptomatic congestive heart failure, any form of
                  substance abuse or psychiatric illness/social situations that would limit
                  compliance with study visits or requirements or a condition that could invalidate
                  communication with the investigator.

               -  Subject is known to be positive for human immunodeficiency virus, hepatitis B
                  surface antigen, hepatitis B core immunoglobulin or immunoglobulin G (IgG)
                  antibody or hepatitis C (IgG or ribonucleic acid (RNA) test) indicating acute or
                  chronic infection.

               -  Subject has a history of moderate to severe ascites, clinically significant
                  and/or rapidly accumulating ascites, bleeding esophageal varices, hepatic
                  encephalopathy or pericardial and/or pleural effusions related to liver
                  insufficiency within 6 months of screening. Mild ascites that does not preclude
                  safe IT injection of ASP9801 is allowed.

               -  Subject has a clinically significant abnormal electrocardiogram (ECG) at
                  screening.

               -  Subject has symptomatic cardiovascular disease within the preceding 12 months
                  unless cardiology consultation and clearance has been obtained for study
                  participation, including but not limited to the following: significant coronary
                  artery disease (e.g., requiring angioplasty or stenting), acute myocardial
                  infarction or unstable angina pectoris < 3 months prior to screening,
                  uncontrolled hypertension, clinically significant arrhythmia or congestive heart
                  failure (New York Heart Association grade ≥ 2).

               -  Subject has medical conditions that predispose the subject to untoward medical
                  risk in the event of volume loading (e.g., intravenous fluid bolus infusion),
                  tachycardia or hypotension during or following treatment with ASP9801.

               -  Subject has a known or suspected hypersensitivity to ASP9801 or any components of
                  the formulation used, including prior adverse reaction to vaccinia (e.g., as
                  smallpox vaccine).

               -  Subject has had previous exposure with ASP9801.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicities (DLT) - dose escalation part
Time Frame:Up to 28 days
Safety Issue:
Description:Incidence of dose limiting toxicities

Secondary Outcome Measures

Measure:Percent change from baseline in antitumor activity of ASP9801
Time Frame:Up to 12 months
Safety Issue:
Description:Percent change from baseline in sum of diameters of injected tumors per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and immune modified response evaluation criteria in solid tumors (imRECIST)
Measure:Objective Response Rate
Time Frame:Up to 12 months
Safety Issue:
Description:Partial Response (PR) + Complete Response (CR) per imRECIST
Measure:ASP9801 viral DNA in blood
Time Frame:Up to 12 months
Safety Issue:
Description:Viral DNA load will be summarized by cohort using descriptive statistics.
Measure:Viral shedding of ASP9801 in saliva
Time Frame:Up to 12 months
Safety Issue:
Description:Viral DNA will be analyzed by quantitative polymerase chain reaction (qPCR).
Measure:Viral shedding of ASP9801 in urine
Time Frame:Up to 12 months
Safety Issue:
Description:Viral DNA will be analyzed by qPCR.
Measure:Viral shedding of ASP9801 in skin (cutaneous/subcutaneous only)
Time Frame:Up to 12 months
Safety Issue:
Description:Viral DNA will be analyzed by qPCR.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Astellas Pharma Global Development, Inc.

Trial Keywords

  • immunotherapy
  • vaccinia virus
  • visceral lesions
  • cutaneous lesions
  • intratumoral injection
  • ASP9801
  • subcutaneous lesions
  • oncolytic virus

Last Updated

April 5, 2021